Nodding Syndrome is a brain seizure disorder found in hotspots in sub-Saharan Africa, including Mundri County, Western Equatoria Province, South Sudan, the setting of the proposed epidemiological study. Children typically develop an uncontrollable, rhythmic nodding of the head shortly after beginning to eat their local diet, a phenomenon termed eating seizures/epilepsy. With time, head nodding may advance to tonic-clonic seizures, wasting, and cognitive deficits, eventually with a fatal outcome. Preliminary studies show that Nodding Syndrome is associated with skin infection with the nematode worm Onchocerca volvulus, the cause of onchocerciasis (River Blindness), but additional local environmental factors must participate because, in other parts of Africa, onchocerciasis is variably associated with epilepsy and rarely with Nodding Syndrome. We hypothesize that plant and/or fungal toxins in food, in the presence or absence of specific nutritional deficiencies, contribute in triggering eating epilepsy in children with Nodding Syndrome. We will test this hypothesis in a cohort of 1000 eligible subjects (males and females, aged 5-21 years), from which we will select 50 subjects with Nodding Syndrome (Cases) and 100 subjects with no history of head nodding or other seizure types (absence, grand mal) (Controls). We will carry out this nested Case:Control study of Nodding Syndrome to examine the relative contributions of exposure to environmental factors associated with epilepsy and other convulsive disorders. These include infectious agents (Onchocerca volvulus), nutritional status (vitamin B6, zinc), plant toxins (cyanogens) and fungal toxins (tremorgens, ergot). These factors will be analyzed in food, blood and urine collected from Cases and Controls and analyzed with respect to Nodding Syndrome. The results will be shared with families, community and health authorities. Recommendations will be made on food preparation and storage to minimize exposure to plant and fungal agents that may trigger seizure activity and thereby advance brain damage. Discovery that plant/fungal toxins can promote seizures in individuals prone to epileptic attacks would have relevance in the prevention and treatment of epileptic disorders worldwide.